This Week in Science

Science  07 Dec 2018:
Vol. 362, Issue 6419, pp. 1124
  1. Cancer

    A systematic look at a childhood tumor

    1. Paula A. Kiberstis

    Fluorescence imaging of highly motile neuroblastoma cells in a mouse model


    Neuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly variable. Some neuroblastomas are fatal despite treatment, whereas others respond well to treatment and some undergo spontaneous regression without treatment. Ackermann et al. sequenced more than 400 pretreatment neuroblastomas and identified molecular features that characterize the three distinct clinical outcomes. Low-risk tumors lack telomere maintenance mechanisms, intermediate-risk tumors harbor telomere maintenance mechanisms, and high-risk tumors harbor telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations.

    Science, this issue p. 1165

  2. Microbiology

    Actively persistent Salmonella

    1. Caroline Ash

    A proportion of Salmonella cells can enter a reversible state of growth arrest, which allows them to tolerate environmental stress such as antibiotics. Stapels et al. found that these cells are not dormant but are actively modulating their environment. Salmonella within their host macrophage niche deployed a specialized type 3 secretory system called SPI-2 to deliver virulence factors, including SteE, into host cells. SteE changed the cytokine profile of the infected macrophages to reprogram them into a noninflammatory and infection-permissive state. Thus, when antibiotics were removed, the Salmonella could reemerge and cause disease.

    Science, this issue p. 1156

  3. Human Genetics

    Genetic architecture of developmental disorders

    1. Laura M. Zahn

    The genetics of developmental disorders (DDs) is complex. Martin et al. wanted to determine the degree of recessive inheritance of DDs in protein-coding genes. They examined the exomes of more than 6000 families in populations with high and low proportions of consanguineous marriages. They found that 3.6% of DDs in individuals of European ancestry involved recessive coding disorders, less than a tenth of the levels previously estimated. Furthermore, among South Asians with high parental relatedness, rather than most of the disorders arising from inherited variants, fewer than half had a recessive coding diagnosis.

    Science, this issue p. 1161

  4. Molecular Biology

    DNA methylation promotes transcription

    1. Steve Mao

    DNA methylation generally represses transcription, but in some instances, it has also been implicated in transcription activation. Harris et al. identified a protein complex in Arabidopsis that is recruited to chromatin by DNA methylation. This complex specifically activated the transcription of genes that are already mildly transcribed but had no effect on transcriptionally silent genes such as transposable elements. The complex thereby counteracts the repression effect caused by transposon insertion in neighboring genes while leaving transposons silent. Thus, by balancing both repressive and activating transcriptional effects, DNA methylation can act to fine-tune gene expression.

    Science, this issue p. 1182

  5. Materials Science

    Tunable materials respond to magnetic field

    1. Philippa J. Benson

    Although certain four-dimensional (4D) printed materials can respond to external stimuli, these are hard to control or feature long response times. Jackson et al. created tunable materials that can respond to an applied magnetic field by incorporating liquids that contain ferromagnetic microparticles into 3D-printed polymer tubes. In tests, these structures responded to a magnetic field in under a second. The approach could see broad applications in fields that include soft robotics, transportation systems, and smart wearable technology.

    Sci. Adv. 10.1126/sciadv.aau6419 (2018).

  6. Immunology

    Optimal affinity

    1. Christiana N. Fogg

    Germinal center (GC) B cells are essential to generating protective antibody responses and are selected through a process of affinity maturation. Kwak et al. now define intrinsic properties of human GC B cells that are critical to antigen affinity discrimination. They identified B cell antigen receptor–containing actin-rich pod-like structures that facilitated formation of highly stable immunological synapses and antigen internalization when GC B cells engaged high-affinity antigens. These structures were important in setting thresholds for affinity selection and driving GC B cell responses.

    Sci. Immunol. 3, eaau6598 (2018).

  7. Computer Science

    One program to rule them all

    1. Jelena Stajic

    Computers can beat humans at increasingly complex games, including chess and Go. However, these programs are typically constructed for a particular game, exploiting its properties, such as the symmetries of the board on which it is played. Silver et al. developed a program called AlphaZero, which taught itself to play Go, chess, and shogi (a Japanese version of chess) (see the Editorial, and the Perspective by Campbell). AlphaZero managed to beat state-of-the-art programs specializing in these three games. The ability of AlphaZero to adapt to various game rules is a notable step toward achieving a general game-playing system.

    Science, this issue p. 1140; see also pp. 1087 and 1118

  8. Batteries

    Working toward fluoride batteries

    1. Marc S. Lavine

    Owing to the low atomic weight of fluorine, rechargeable fluoride-based batteries could offer very high energy density. However, current batteries need to operate at high temperatures that are required for the molten salt electrolytes. Davis et al. push toward batteries that can operate at room temperature, through two advances. One is the development of a room-temperature liquid electrolyte based on a stable tetraalkylammonium salt–fluorinated ether combination. The second is a copper–lanthanum trifluoride core-shell cathode material that demonstrates reversible partial fluorination and defluorination reactions.

    Science, this issue p. 1144

  9. Quantum Materials

    Twisting a route for surface plasmons

    1. Ian S. Osborne

    Graphene is an atomically thin material that supports highly confined plasmon polaritons, or nano-light, with very low loss. The properties of graphene can be made richer by introducing and then rotating a second layer so that there is a slight angle between the atomic registry. Sunku et al. show that the moiré patterns that result from such twisted bilayer graphene also provide confined conducting channels that can be used for the directed propagation of surface plasmons. Controlling the structure thereby provides a pathway to control and route surface plasmons for a nanophotonic platform.

    Science, this issue p. 1153

  10. Carbon Cycle

    Animals count

    1. Sacha Vignieri

    Flux across the carbon cycle is generally characterized by contributions from plants, microbes, and abiotic systems. Animals, however, move vast amounts of carbon, both through ecosystem webs and across the landscape. Schmitz et al. review the different contributions that animal populations make to carbon cycling and discuss approaches that allow for better monitoring of these contributions.

    Science, this issue p. eaar3213

  11. Human Genomics

    Complex processes in the settling of the Americas

    1. Laura M. Zahn

    The expansion into the Americas by the ancestors of present day Native Americans has been difficult to tease apart from analyses of present day populations. To understand how humans diverged and spread across North and South America, Moreno-Mayar et al. sequenced 15 ancient human genomes from Alaska to Patagonia. Analysis of the oldest genomes suggests that there was an early split within Beringian populations, giving rise to the Northern and Southern lineages. Because population history cannot be explained by simple models or patterns of dispersal, it seems that people moved out of Beringia and across the continents in a complex manner.

    Science, this issue p. eaav2621

  12. Antimalarials

    A path to tackle liver-stage parasites

    1. Caroline Ash

    Malaria parasites are evolutionarily prepared to resist drug attack. Resistance is emerging to even the latest frontline combination therapies, which target the blood stages of the Plasmodium parasite. As an alternative strategy, Antonova-Koch et al. investigated the possibilities of drugs against liver-stage parasites (see the Perspective by Phillips and Goldberg). To do so, they devised a luciferase-reporter drug screen for the rodent parasite Plasmodium berghei. Three rounds of increasingly stringent screening were used. From this regime, several chemotypes that inhibit Plasmodium mitochondrial electron transport were identified. Excitingly, several new scaffolds, with as-yet-unknown modes of action but solely targeting the parasites' liver stages, emerged as promising drug leads for further development.

    Science, this issue p. eaat9446; see also p. 1112

  13. Nanomaterials

    No barriers to growing a row

    1. Phil Szuromi

    Classical nucleation theory predicts that two-dimensional islands on a surface must reach a critical size before they continue to grow; below that size, they dissolve. Chen et al. used phage display to select for short peptides that would bind to molybdenum disulfide (MoS2) (see the Perspective by Kahr and Ward). Hexagonal arrays of these peptides grew epitaxially as dimers but without a size barrier—the critical nuclei size was zero. Although two-dimensional arrays formed, growth occurred one row at time. Classical nucleation theory indeed predicts the absence of a barrier for such one-dimensional growth.

    Science, this issue p. 1135; see also p. 1111

  14. Climate Impacts

    Drivers of the “Great Dying”

    1. Sacha Vignieri

    Though our current extinction crisis is substantial, it pales in comparison to the largest extinction in Earth's history, which occurred at the end of the Permian Period. Referred to as the “Great Dying,” this event saw the loss of up to 96% of all marine species and 70% of terrestrial species. Penn et al. explored the extinction dynamics of the time using Earth system models in conjunction with physiological data across animal taxa (see the Perspective by Kump). They conclude that increased marine temperatures and reduced oxygen availability were responsible for a majority of the recorded extinctions. Because similar environmental alterations are predicted outcomes of current climate change, we would be wise to take note.

    Science, this issue p. eaat1327; see also p. 1113

  15. Polymers

    Beating the heat by blending

    1. Phil Szuromi

    Charge carriers move through semiconductor polymers by hopping transport. In principle, these polymers should be more conductive at higher temperatures. In practice, conductivity drops at high temperatures because interchain contacts are disrupted, which limits potential applications. Gumyusenge et al. now show that appropriate blending of a semicrystalline conjugated polymer with an insulating polymer that has a high glass-transition temperature creates a morphology that stabilizes a network of semiconductor channels. High charge conductivity was maintained in these materials up to 220°C.

    Science, this issue p. 1131

  16. Valleytronics

    Making a practical valleytronics device

    1. Jelena Stajic

    Two-dimensional materials with a hexagonal lattice, such as graphene, have two distinct “valleys” in their band structure. Researchers in the emerging field of valleytronics hope that these valley degrees of freedom can be exploited as information carriers, but making valleytronic devices is tricky. Li et al. created chiral valley Hall states on the boundary between oppositely gated regions of bilayer graphene. They then guided these so-called kink states through their sample using spatially modulated gating, demonstrating right and left turns, as well as a valley valve function.

    Science, this issue p. 1149

  17. Biophysics

    How membrane viscosity affects respiration

    1. L. Bryan Ray

    In bacteria, energy production by the electron transport chain occurs at cell membranes and can be influenced by the lipid composition of the membrane. Budin et al. used genetic engineering to influence the concentration of unsaturated branched-chain fatty acids and thus control membrane viscosity (see the Perspective by Schon). Experimental measurements and mathematical modeling indicated that rates of respiratory metabolism and rates of cell growth were dependent on membrane viscosity and its effects on diffusion. Experiments on yeast mitochondria also showed similar effects. Maintaining efficient respiration may thus place evolutionary constraints on cellular lipid composition.

    Science, this issue p. 1186; see also p. 1114

  18. Regeneration

    Do endothelial cells hold the key to success?

    1. Gemma Alderton

    Endothelial cells line the inner vascular wall, and their phenotype and behavior can vary according to the organ in which they are situated and the environment. Not only do endothelial cells form the barrier of vessel walls, they also can participate in signaling with the surrounding tissue to promote regeneration and growth. In a Perspective, Gomez-Salinero and Rafii discuss how endothelial cells contribute to wound healing, regeneration, and disease states, such as cancer, and how our growing understanding of endothelial cell plasticity might advance regenerative medicine and the development of artificial organs for transplant.

    Science, this issue p. 1116

  19. Signal Transduction

    Regulation of RAS by ubiquitination

    1. L. Bryan Ray

    The protein LZTR1 is mutated in human cancers and developmental diseases. Work from two groups now converges to implicate the protein in regulating signaling by the small guanosine triphosphatase RAS. Steklov et al. showed that mice haploinsufficient for LZTR1 recapitulated aspects of the human disease Noonan syndrome. Their biochemical studies showed that LZTR1 associated with RAS. LZTR1 appears to function as an adaptor that promotes ubiquitination of RAS, thus inhibiting its signaling functions. Bigenzahn et al. found LZTR1 in a screen for proteins whose absence led to resistance to the tyrosine kinase inhibitors used to treat cancers caused by the BCR-ABL oncogene product. Their biochemical studies and genetic studies in fruitflies also showed that loss of LZTR1 led to increased activity of RAS and signaling through the mitogen-activated protein kinase pathway.

    Science, this issue p. 1177, p. 1171

  20. Cancer

    Expanding the landscape of immunotherapy targets

    1. Catherine A. Charneski

    Most searches for druggable tumor-specific antigens (TSAs) start with an examination of peptides derived from protein-coding exons. Laumont et al. took a different approach and found numerous TSAs that derived from aberrant expression of noncoding sequences in murine cell lines and in B-lineage acute lymphoblastic leukemia and lung cancer patient samples. They validated the immunogenicity and efficacy of TSA vaccination for select antigens in mouse models of cancer. Noncoding regions are a potentially rich source of TSAs that could greatly expand the number of targetable antigens across different cancers, including those with low mutational burdens.

    Sci. Transl. Med. 10, eaau5516 (2018).

  21. Cell Biology

    Cleaving a different function for p62

    1. Wei Wong

    The scaffold protein p62 has a critical role in autophagy, the regulated intracellular degradation of proteins and organelles. Sanchez-Garrido et al. identified a proteolytic fragment of human p62, called p62TRM, that had a distinct function from full-length p62 (see the Focus by Martens). Instead of promoting autophagy, p62TRM regulated responses to nutrient availability. This function was lost in p62 variants with disease-associated mutations in the cleavage site, suggesting that defective nutrient sensing may account for some of the symptoms of patients with p62 mutations.

    Sci. Signal. 11, eaat6903, eaav3530 (2018).

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